Effect of <i>CYP3A5*3</i> genotype on serum carbamazepine concentrations at steady-state in Korean epileptic patients

Park, P.-W.,Seo, Y. H.,Ahn, J. Y.,Kim, K.-A.,Park, J.-Y. Blackwell Publishing Ltd 2009 Journal of clinical pharmacy and therapeutics Vol.34 No.5

<P>Abstract</P><P>Background and Objective: </P><P>Carbamazepine (CBZ) is metabolized mainly by the CYP3A family of enzymes, which includes CYP3A4 and CYP3A5. Several studies have suggested that the <I>CYP3A5*3</I> genotype influences the pharmacokinetics of CYP3A substrates. The present study aimed to assess the effect of the <I>CYP3A5*3</I> genotype on serum concentration of CBZ at the steady-state in Korean epileptic patients.</P><P>Method: </P><P>The serum concentrations of CBZ in 35 Korean epileptic patients were measured and their <I>CYP3A5</I> genotype was determined. Fourteen patients were <I>CYP3A5</I> expressors (two for <I>CYP3A5*1/*1</I> and 12 for <I>CYP3A5*1/*3</I>) and 21 patients were <I>CYP3A5</I> non-expressors (<I>CYP3A5*3/*3</I>). Dose-normalized concentrations (mean ± SD) of CBZ were 9·9 ± 3·4 ng/mL/mg for <I>CYP3A5</I> expressors and 13·1 ± 4·5 ng/mL/mg for <I>CYP3A5</I> non-expressors (<I>P</I> = 0·032). The oral clearance of CBZ was significantly higher in <I>CYP3A5</I> non-expressors than that of <I>CYP3A5</I> expressors (0·056 ±0·017 L/h/kg vs. 0·040 ± 0·014 L/h/kg, <I>P</I> = 0·004). The <I>CYP3A5</I> genotype affected the CBZ concentrations in Korean epileptic patients and is a factor that may contribute to inter-individual variability in CBZ disposition in epileptic patients.</P>

Pharmacodynamic Effect of Cilostazol Plus Standard Clopidogrel Versus Double-Dose Clopidogrel in Patients With Type 2 Diabetes Undergoing Percutaneous Coronary Intervention

Jeong, Young-Hoon,Tantry, Udaya S.,Park, Yongwhi,Kwon, Tae Jung,Park, Jeong Rang,Hwang, Seok-Jae,Bliden, Kevin P.,Koh, Eun-Ha,Kwak, Choong Hwan,Hwang, Jin-Yong,Kim, Sunjoo,Gurbel, Paul A. American Diabetes Association 2012 Diabetes care Vol.35 No.11

<P><B>OBJECTIVE</B></P><P>To determine the effect of adding cilostazol (100 mg b.i.d.) to standard-dose clopidogrel (75 mg/d) (TRIPLE) compared with double-dose clopidogrel (150 mg/d) (DOUBLE) and the influence of the cytochrome P450 (<I>CYP2C19*2/*3</I>, <I>CYP3A5*3)</I>and ATP-binding cassette subfamily B1(<I>ABCB1 C3435T</I>) genetic polymorphisms in type 2 diabetes (T2DM) patients.</P><P><B>RESEARCH DESIGN AND METHODS</B></P><P>T2DM patients were treated with TRIPLE (<I>n</I> = 41) or DOUBLE (<I>n</I> = 39) after percutaneous coronary intervention. Conventional aggregometry and VerifyNow were performed at baseline and at 30 days. The primary end point was absolute change in 20-μM ADP-induced maximal platelet aggregation (ΔMPA<SUB>20</SUB>) between baseline and switching values.</P><P><B>RESULTS</B></P><P>TRIPLE versus DOUBLE showed greater ΔMPA<SUB>20</SUB> (22.9 ± 11.6 vs.12.7 ± 15.5%; difference, 10.2% [95% CI 4.2–16.3]; <I>P</I> < 0.001). Carriage of one (β coefficient, −5.4%; <I>P</I> = 0.162) and two <I>CYP2C19</I> loss-of-function allele(s) (−8.3%; <I>P</I> = 0.007) were associated with lower ΔMPA<SUB>20</SUB> in DOUBLE–treated patients, but not in TRIPLE-treated patients.</P><P><B>CONCLUSIONS</B></P><P>Among T2DM patients, adding cilostazol achieves greater platelet inhibition compared with clopidogrel (150 mg/d), which is not influenced by genetic polymorphisms.</P>

Unraveling the Atomistic Sodiation Mechanism of Black Phosphorus for Sodium Ion Batteries by First-Principles Calculations

Hembram, K. P. S. S.,Jung, Hyun,Yeo, Byung Chul,Pai, Sung Jin,Kim, Seungchul,Lee, Kwang-Ryeol,Han, Sang Soo American Chemical Society 2015 The Journal of Physical Chemistry Part C Vol.119 No.27

<P>As opposed to the standard graphite anode used for lithium (Li) ion batteries (LIBs), a standard anode material for sodium (Na) ion batteries (NIBs) has not yet been reported. Black phosphorus is potentially very attractive as an anode material for NIBs, as it has a layered structure similar to graphite but a greater interlayer distance. In this work, we propose an atomistic mechanism for the sodiation of black phosphorus, based on first-principles calculations. The layered structure of black phosphorus is maintained up to the composition of Na<SUB>0.25</SUB>P, with <I>one-dimensional</I> sodiation (an intercalation process) occurring in the interlayer spaces of the black phosphorus, resulting in sliding of the phosphorene layers because one Na atom tends to bind to four P atoms. At Na levels beyond Na<SUB>0.25</SUB>P, the intercalation process changes to an alloying process. Sodiation exceeding the critical composition leads to breaking of P–P bonds and eventual formation of an amorphous phase from the layered Na<SUB><I>x</I></SUB>P structure. After the P–P bonds in the layered Na<SUB><I>x</I></SUB>P structure are broken, in a progress in which staggered P–P bonds are preferentially broken rather than planar P–P bonds, P<SUB>2</SUB> dumbbells are generated. As sodiation proceeds further, most of the P<SUB>2</SUB> dumbbells become isolated P atoms. Thus, in the amorphous Na<SUB>3</SUB>P phase, only low-coordinate P components such as isolated atoms (primarily) and dumbbells are found. We expect that our comprehensive understanding of the sodiation mechanism in black phosphorus will provide helpful guidelines in designing new types of black phosphorus anodes to obtain better performing NIBs.</P><P><B>Graphic Abstract</B> <IMG SRC='http://pubs.acs.org/appl/literatum/publisher/achs/journals/content/jpccck/2015/jpccck.2015.119.issue-27/acs.jpcc.5b05482/production/images/medium/jp-2015-054822_0006.gif'></P><P><A href='http://pubs.acs.org/doi/suppl/10.1021/jp5b05482'>ACS Electronic Supporting Info</A></P>

<i>In vitro</i> inhibitory effects of Wen‐pi‐tang‐Hab‐Wu‐ling‐san on human cytochrome P450 isoforms

Lee, H. W.,Kim, D. W.,Phapale, P. B.,Lim, M. ‐,S.,Park, J.,Seo, J. J.,Park, K. M.,Park, Y. ‐,K.,Yoon, Y. ‐,R. Blackwell Publishing Ltd 2011 Journal of clinical pharmacy and therapeutics Vol.36 No.4

<P><B>Summary</B></P><P><B>What is known and Objective: </B> Although Wen‐pi‐tang‐Hab‐Wu‐ling‐san (WHW), an oriental herbal medicine, has been prescribed for the treatment of chronic renal failure (CRF) in Korean clinics, no studies regarding WHW–drug interactions had been reported. The purpose of this study was to evaluate the possibility that WHW inhibits the catalytic activities of major cytochrome P450 (CYP) isoforms.</P><P><B>Methods: </B> The abilities of various WHW extracts to inhibit phenacetin O‐de‐ethylation (CYP1A2), tolbutamide 4‐methylhydroxylation (CYP2C9), omeprazole 4′‐hydroxylation (CYP2C19), dextromethorphan O‐demethylation (CYP2D6), chlorzoxazone 6‐hydroxylation (CYP2E1) and midazolam 1‐hydroxylation (CYP3A4) were assessed using human liver microsomes.</P><P><B>Results and Discussion: </B> WHW extract at concentrations up to 100 μ<SMALL>m</SMALL> showed negligible inhibition of the six CYP isoforms tested (CYP1A2, CYP2C9, CYP2C19, CYP2D6, CYP2E1 and CYP3A4), with apparent IC<SUB>50</SUB> values (concentration of the inhibitor causing 50% inhibition of the original enzyme activity) of 817.5, 601.6, 521.7, 310.2, 342.8 and 487.0 μg/mL, respectively.</P><P><B>What is new and Conclusion: </B> Our <I>in vitro</I> findings suggest that WHW extract at concentrations corresponding to a clinically recommended dosage range has no notable inhibitory effects on CYP isoforms. Therefore, we believe that WHW extract may be free of drug–herb interactions when co‐administered with other medicines. However, <I>in vivo</I> human studies are needed to confirm these results.</P>

Effects of brush-anode configurations on performance and electrochemistry of microbial fuel cells

Kang, Heunggu,Jeong, Jaesik,Gupta, Prabuddha L.,Jung, Sokhee P. Elsevier 2017 International journal of hydrogen energy Vol.42 No.45

<P><B>Abstract</B></P> <P>For practical implementation of MFC, increasing power generation is important because it is closely related with energy production rate and wastewater treatability. However, it is not known which relative arrangement of anode and cathode gives the best performance, and it is necessary to know electrochemical reference point of the brush anode for this. Five different brush-anode configurations were tested in a single-chambered cubic MFC. By merely changing a brush anode configuration, power and current densities were increased by 20% and 30%, respectively. The horizontally-positioned anode configuration (H1) with the closest anode-cathode distance produced the highest power and current. EIS showed that anode impedance and full-cell impedance were decreased by 60% and 49%, respectively. CE and EE were not significantly affected by the anode-cathode distance, but the horizontal type cells showed relatively higher CE, EE and COD removal rate and shorter batch time. The center of a titanium current collector and the center of carbon fibers of a brush-anode were found to be statistically-significant reference points for MFC electrochemistry.</P> <P><B>Highlights</B></P> <P> <UL> <LI> By merely changing anode configuration, P<SUB>max</SUB> increased by 20%. </LI> <LI> By merely changing anode configuration, I<SUB>opt</SUB> increased by 30%. </LI> <LI> Anode impedance and full-cell impedance decreased by 60% and 49%, respectively. </LI> <LI> The horizontal anode with closest electrode distance produced the highest power and current. </LI> <LI> The center of a titanium current collector and the center of carbon fibers were statistically-significant reference points. </LI> </UL> </P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>

Serine palmitoyltransferase inhibitor myriocin induces growth inhibition of B16F10 melanoma cells through G₂/M phase arrest

Lee, Y.‐,S.,Choi, K.‐,M.,Choi, M.‐,H.,Ji, S.‐,Y.,Lee, S.,Sin, D.‐,M.,Oh, K.‐,W.,Lee, Y.‐,M.,Hong, J.‐,T.,Yun, Y.‐,P.,Yoo, H.‐,S. Blackwell Publishing Ltd 2011 Cell proliferation Vol.44 No.4

<P><B>Abstract</B></P><P><B>Objectives: </B> Melanoma is the most aggressive form of skin cancer, and it resists chemotherapy. Candidate drugs for effective anti‐cancer treatment have been sought from natural resources. Here, we have investigated anti‐proliferative activity of myriocin, serine palmitoyltransferase inhibitor, in the <I>de novo</I> sphingolipid pathway, and its mechanism in B16F10 melanoma cells.</P><P><B>Material and methods: </B> We assessed cell population growth by measuring cell numbers, DNA synthesis, cell cycle progression, and expression of cell cycle regulatory proteins. Ceramide, sphingomyelin, sphingosine and sphingosine‐1‐phosphate levels were analysed by HPLC.</P><P><B>Results: </B> Myriocin inhibited proliferation of melanoma cells and induced cell cycle arrest in the G<SUB>2</SUB>/M phase. Expressions of cdc25C, cyclin B1 and cdc2 were decreased in the cells after exposure to myriocin, while expression of p53 and p21<SUP>waf1/cip1</SUP> was increased. Levels of ceramide, sphingomyelin, sphingosine and sphingosine‐1‐phosphate in myriocin‐treated cells after 24 h were reduced by approximately 86%, 57%, 75% and 38%, respectively, compared to levels in control cells.</P><P><B>Conclusions: </B> Our results suggest that inhibition of sphingolipid synthesis by myriocin in melanoma cells may inhibit expression of cdc25C or activate expression of p53 and p21<SUP>waf1/cip1</SUP>, followed by inhibition of cyclin B1 and cdc2, resulting in G<SUB>2</SUB>/M arrest of the cell cycle and cell population growth inhibition. Thus, modulation of sphingolipid metabolism by myriocin may be a potential target of mechanism‐based therapy for this type of skin cancer.</P>

Anti-inflammatory effects of soyasapogenol I-αa via downregulation of the MAPK signaling pathway in LPS-induced RAW 264.7 macrophages

Yang, Seung Hwan,Le, Bao,Androutsopoulos, Vasilis P.,Tsukamoto, Chigen,Shin, Tae-Sun,Tsatsakis, Aristides M.,Chung, Gyuhwa Pergamon 2018 Food and Chemical Toxicology Vol. No.

<P><B>Abstract</B></P> <P>The crude extract of soyasaponins was reported to possess anti-inflammatory activity. We determined the new purity group I saponin, I-αa and I-γa that was isolated from wild soybean (<I>Glycine soja</I>) in terms of its efficacy in protecting RAW 264.7 macrophages from lipopolysaccharide (LPS)-stimuli. Cells were treated with soyasaponin I-αa/I-γa (30–300 μΜ) and LPS (0.1 μg/mL) for 24 h. Soyasaponin I-αa inhibited nitric oxide (NO) production at 100 μg/mL, while soyasaponin I-γa demonstrated this effect at a higher concentration (200 μg/mL). The expression levels of iNOS and COX-2 enzymes were downregulated by both soyasaponins. Soyasaponin I-αa exerted its effect via the TNF-α and IL-1β cytokines. However, soyasaponin I-γa only inhibited the expression of TNF-α. The inflammatory effect of group I soyasaponin was mainly mediated via the phosphorylation of the p38 and JNK proteins. Collectively, these results suggested the potential anti-inflammatory effects of soyasaponins.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Anti-inflammatory effects of a group I saponins from <I>Glycine soja</I> are reported. </LI> <LI> Soyasaponin I-αa inhibited the TNF-α and IL-1β cytokine induced NO generation in RAW 264.7 macrophages. </LI> <LI> Soyasaponin I-γa only inhibited the expression of TNF-α. </LI> <LI> Group I soyasaponin stimulated anti-inflammatory effects via mechanisms related to the p38 and JNK signaling pathways. </LI> </UL> </P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>

Foxp3 is a key downstream regulator of p53-mediated cellular senescence

Kim, J-E,Shin, J-S,Moon, J-H,Hong, S-W,Jung, D-J,Kim, J H,Hwang, I-Y,Shin, Y J,Gong, E-Y,Lee, D H,Kim, S-M,Lee, E Y,Kim, Y S,Kim, D,Hur, D,Kim, T W,Kim, K-p,Jin, D-H,Lee, W-J Macmillan Publishers Limited 2017 Oncogene Vol.36 No.2

<P>The downstream events and target genes of p53 in the process of senescence are not fully understood. Here, we report a novel function of the forkhead transcription factor Foxp3, which is a key player in mediating T-cell inhibitory functions, in p53-mediated cellular senescence. The overexpression of Foxp3 in mouse embryonic fibroblasts (MEFs) accelerates senescence, whereas Foxp3 knockdown leads to escape from p53-mediated senescence in p53-expressing MEFs. Consistent with these results, Foxp3 expression resulted in the induction of senescence in epithelial cancer cells, including MCF7 and HCT116 cells. Foxp3 overexpression also increased the intracellular levels of reactive oxygen species (ROS). The ROS inhibitor N-acetyl-L-cysteine rescued cells from Foxp3-expression-induced senescence. Furthermore, the elevated ROS levels that accompanied Foxp3 overexpression were paralleled by an increase in p21 expression. Knockdown of p21 in Foxp3-expressing MEFs abrogated the Foxp3-dependent increase in ROS levels, indicating that Foxp3 acts through the induction of p21 and the subsequent ROS elevation to trigger senescence. Collectively, these results suggest that Foxp3 is a downstream target of p53 that is sufficient to induce p21 expression, ROS production and p53-mediated senescence.</P>

High performance photodiodes based on chemically processed Cu doped SnS₂ nanoflakes

Mohan Kumar, G.,Xiao, Fu,Ilanchezhiyan, P.,Yuldashev, Sh.,Madhan Kumar, A.,Cho, H.D.,Lee, D.J.,Kang, T.W. Elsevier 2018 APPLIED SURFACE SCIENCE - Vol.455 No.-

<P><B>Abstract</B></P> <P>In this work, Cu doped SnS<SUB>2</SUB> nanoflakes were synthesized through a simple hydrothermal method. The influence of Cu doping on the structural, optical and electrical properties of SnS<SUB>2</SUB> were investigated in detail. Optical properties explores the Cu doping in SnS<SUB>2</SUB> crystal lattice to result with a red-shift in absorption spectrum, which benefits visible-light absorption. Photodiodes were further fabricated by spin coating Cu doped SnS<SUB>2</SUB> nanoflakes on p-type silicon (Si). Electrical and photoelectrical parameters of Cu doped SnS<SUB>2</SUB> nanoflakes were determined by studying their impedance and current–voltage (I–V) characteristics, respectively. The diodes were found to exhibit excellent rectifying behavior and good sensitivity on par to pristine photodiodes. Impedance results identified the resistance of device to reduce considerably on Cu doping. The enhanced photoelectrical properties of the heterojunctions has been ascribed to Cu ions, which act as effective dopant and contribute to the varied carrier concentration in SnS<SUB>2</SUB>. Finally the obtained results suggest the potential of Cu-doped SnS<SUB>2</SUB> for application in photodetection and sensors applications.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Cu doped SnS<SUB>2</SUB> nanoflakes were synthesized in hexagonal phase. </LI> <LI> Nature of charge carriers/carrier density was determined using Mott-Schottky plots. </LI> <LI> Photodiode based on Cu doped SnS<SUB>2</SUB> nanoflakes were fabricated on p-Si substrate. </LI> <LI> Photodiode revealed improved photocurrent and responsitivity values under illumination. </LI> </UL> </P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>

Development of multifunctional metabolic synergists to suppress the evolution of resistance against pyrethroids in insects that blood feed on humans

Hardstone, Melissa C,Strycharz, Joseph P,Kim, Junheon,Park, Il‐,Kwon,Yoon, Kyong Sup,Ahn, Young Joon,Harrington, Laura C,Lee, Si Hyeock,Clark, J Marshall John Wiley Sons, Ltd 2015 Pest Management Science Vol.71 No.6

<P><B>Abstract</B></P><P><B>BACKGROUND</B></P><P>Pyrethroids are the insecticides of choice when exposure to humans is likely, such as occurs in vector and public‐health‐related control programs. Unfortunately, the pyrethroids share a common resistance mechanism with dichlorodiphenyltrichloroethane (DDT), knockdown resistance (<I>kdr</I>), and prior extensive use of DDT has predisposed the pyrethroids to cross‐resistance via <I>kdr</I>. Given the widespread occurrence of <I>kdr</I>, the use of synergists with pyrethroids is considered to be prudent to guard against the selection of multiply resistant insects.</P><P><B>RESULTS</B></P><P>3‐Phenoxybenzyl hexanoate (PBH) was synthesized as a multifunctional pyrethroid synergist that, besides being a surrogate substrate for sequestration/hydrolytic carboxylesterases, now also functions as a substrate for oxidative xenobiotic metabolism. The addition of PBH to permethrin‐treated females of the ISOP450 strain of <I>Culex pipiens quinquefasciatus</I> resulted in a threefold increase in synergism, as judged by the synergistic ratio. Similarly, PBH synergized the action of deltamethrin sixfold on females of the common bed bug, <I>Cimex lectularius</I>, and was 2.8‐fold more synergistic than piperonyl butoxide (PBO).</P><P><B>CONCLUSIONS</B></P><P>PBH synergized the action of both type I and type II pyrethroids in a mosquito vector (<I>Cx. p. quinquefasciatus</I>) and in a public‐health pest, <I>C. lectularius</I>, respectively, indicating a broad spectrum of action on blood‐feeding insects. PBH appears to have residual properties similar to permethrin and is itself non‐toxic, unlike PBO, and therefore should be compatible with existing pyrethroid formulations used for insecticide‐treated nets and home/residential sprays. © 2014 Society of Chemical Industry</P>